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Current Molecular Pharmacology


ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

Review Article

Inactivation of Parathyroid Hormone: Perspectives of Drug Discovery to Combating Hyperparathyroidism

Author(s): Amit Kumar* and Jochen Balbach*

Volume 15, Issue 2, 2022

Published on: 26 January, 2021

Article ID: e170322190727 Pages: 14

DOI: 10.2174/1874467214666210126112839

Price: $65


Hormonal coordination is tightly regulated within the human body and thus regulates human physiology. The parathyroid hormone (PTH), a member of the endocrine system, regulates the calcium and phosphate level within the human body. Under non-physiological conditions, PTH levels get upregulated (hyperparathyroidism) or downregulated (hypoparathyroidism) due to external or internal factors. In case of hyperparathyroidism, elevated PTH stimulates cellular receptors present in the bones, kidneys, and intestines to increase the blood calcium level, leading to calcium deposition. This eventually causes various symptoms, including kidney stones. Currently, there is no known medication that directly targets PTH in order to suppress its function. Therefore, it is of great interest to find novel small molecules or any other means that can modulate PTH function. The molecular signaling of PTH starts by binding its N-terminus to the G-protein coupled PTH1/2 receptor. Therefore, any intervention that affects the N-terminus of PTH could be a lead candidate for treating hyperparathyroidism. As a proof-of-concept, there are various possibilities to inhibit molecular PTH function by (i) a small molecule, (ii) N-terminal PTH phosphorylation, (iii) fibril formation and (iv) residue-specific mutations. These modifications put PTH into an inactive state, which will be discussed in detail in this review article. We anticipate that exploring small molecules or other means that affect the N-terminus of PTH could be lead candidates in combating hyperparathyroidism.

Keywords: Hormone function, hyperparathyroidism treatment, PTH hormone, small molecules, protein phosphorylation, amyloid formation.

Graphical Abstract
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